36 results about "Animal genome" patented technology

Provided in the present invention are a non-human animal expressing a human or chimeric (e.g. humanized) CFB protein and a use method thereof. Further provided in the present invention are a non-human animal genome, a humanized CFB gene, and a cell, tissue, organ or non-human animal containing the non-human animal genome and the humanized CFB gene. The non-human animal obtained by the present application successfully expresses the human or humanized CFB protein, wherein the protein can be cleaved by CFD, bind to C3b, and achieve a similar effect as in a human body. In addition, the non-human animal obtained in the present application has a complete renal function state and normal blood biochemical indexes. Even more rarely, potential diseases known in the prior art which have been observed in some other transgenic mice do not occur in the non-human animal.

The present invention relates to genetically modified non-human animals expressing human EPO. Genetically modified non-human animals expressing human EPO from animal genomes are provided. Also provided are methods for generating non-human animals expressing human EPO from non-human animal genomes, and methods for using non-human animals expressing human EPO from non-human animal genomes. These animals and methods have many uses in the art, including, for example, modeling of human erythropoiesis and erythrocyte function; modeling of human pathogen infection of erythrocytes; in vivo screening of agents regulating erythropoiesis and / or erythrocyte function, for example in a healthy or diseased state; screening of agents toxic to erythrocytes or erythrocyte progenitors; in vivo screening of agents that prevent, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in vivo screening of erythrocytes or erythrocyte progenitors from individuals to predict individual responsiveness to disease therapy.

The invention relates to a method for the generation of a TCR in a rodent, method comprising delivering an antigen presenting cell (APC) expressing an MHC-peptide complex to the rodent, wherein the MHC component of the MHC peptide is not expressed and generating T-cells to the MHC-peptide complex in the rodent. The method further comprises isolating or purifying the T-cell from the rodent. The MHC component is either allogenic or xenogenic and the MHC expressed in the rodent is a human HLA, such as HLA-A*02:01, HLA-A*11:01, HLA-A*03:01 or HLA-A*24:02. The rodent genome encodes a fully human TCR. The peptide is from a human antigen associated with disease, such as a tumour associated antigen. The rodent genome comprises human CD8 or chimeric CD8. The TCR sequence has been modified by up to 3 amino acids from that identified in the rodent. Also disclosed is a method for generating a TCR in a mouse, identifying the nucleic acid encoding the TCR and then mutating the sequence. The TCR is expressed in the form of a larger molecule. The APC is a synthetic antigen presenting cell.

The invention discloses a universal molecular beacon kit for various animal-derived components, and belongs to the technical field of molecular biological detection. Aiming at gene segments with specific structural characteristics in 11 common livestock and poultry animal genomes, the invention designs a composition of a universal primer and a molecular beacon fluorescent probe. The combination can be used for carrying out real-time fluorescent PCR detection and melting curve analysis by using the kit and the method by taking genome DNA of a sample to be detected as a template. By comparing the shape of a melting peak of a detected sample and the characteristic melting temperature (Tm value) of the detected sample, 11 animal-derived components of livestock and poultry can be quickly and accurately identified under the condition of single-tube detection. Technical innovation is achieved in the field of molecular biological detection, an efficient and reliable solution is provided for animal-derived component detection, and the method has important practical value and popularization potential.

The invention belongs to the technical field of animal genome editing, and particularly relates to a method for realizing fixed-point integration of full-length exogenous DNA fragments by using long single-stranded DNA. The technical problem to be solved by the invention is to provide a method for efficiently realizing site-specific integration of an exogenous full-length gene in a mammal genome. According to the technical scheme, the method for realizing fixed-point integration of the full-length exogenous DNA fragment by using the long single-stranded DNA comprises the following steps: converting a mixture of sgRNA, Cas9mRNA and / or Cas9 protein of a long single-stranded exogenous gene and guiding Cas9 to cut an integration site into recipient cells; the exogenous gene long single strand comprises a 5'homologous arm and a 3 'homologous arm which are arranged on the upstream and downstream of an sgRNA guide cleavage site, a full-length exogenous DNA fragment sequence arranged between the 5' homologous arm and the 3 'homologous arm, and related matching original parts required by expression of the full-length exogenous DNA fragment sequence.

The invention belongs to the field of transgenic animals, and relates to an MET gene modified non-human animal. Specifically, the present invention provides a method of making a genetically modified non-human animal comprising modifying a non-human animal genome such that the modified non-human animal genome comprises a nucleotide sequence encoding a human or chimeric hepatocyte growth factor receptor (MET) protein. Also provided is a genetically modified non-human animal genome comprising a nucleotide sequence encoding a human or chimeric MET protein. The non-human animal obtained by the method provided by the invention provides a powerful tool for researching the function of the MET protein, and provides a platform for screening related drugs.

The present invention relates to genetically modified non-human animals expressing human EPO. Genetically modified non-human animals that express human EPO from an animal genome are provided. Also provided are methods for generating a non-human animal that expresses human EPO from a non-human animal genome, and methods for using a non-human animal that expresses human EPO from a non-human animal genome. These animals and methods have many uses in the art, including, for example, modeling of human erythropoiesis and erythrocyte function; modeling of human pathogen infection of red blood cells; in vivo screening of agents that modulate erythropoiesis and / or erythrocyte function, for example in a healthy or diseased state; screening agents which are toxic to the red blood cells or red blood cell ancestors; in vivo screening of agents that prevent, mitigate, or reverse toxic effects of toxic agents on red blood cells or red blood cell ancestors; in vivo screening of red blood cells or red blood cell ancestors from an individual to predict responsiveness of the individual to disease therapy.

The present invention provides non-human animals expressing human CFB protein or chimeric (e.g., humanized) CFB protein and methods for using the same. The present invention further provides a non-human animal genome, a humanized CFB gene, and cells, tissues, organs, or non-human animals containing the non-human animal genome and the humanized CFB gene. The non-human animals obtained in this application successfully express human CFB protein or humanized CFB protein, which can be cleaved by CFD, bind to C3b, and exert similar effects in the human body. Furthermore, the non-human animals obtained in this application have complete renal function, normal blood biochemical indicators, and, more remarkably, do not exhibit the potential diseases observed in other transgenic mice known in this art.

The invention relates to a method for constructing a retinitis pigmentosa (RP) animal model. The method comprises the step of introducing a human-derived RPGR gene segment comprising RPGR gene mutation into an animal genome. The invention also relates to the RP animal model constructed by the method and application of the animal model in in-vivo evaluation of efficacy and / or safety of a gene editing drug for treating RP.

Provided are a non-human animal with humanized IL22, IL22RA1, IL10RB, IL20RA, and / or IL20RB genes, or a genome thereof, and use thereof in the field of biomedicine. All or part of the endogenous IL22, IL22RA1, IL10RB, IL20RA, and / or IL20RB genes of the non-human animal are replaced by corresponding human regions to obtain a modified non-human animal genome. The non-human animal comprising the modified non-human animal genome can normally express human or humanized IL22, IL22RA1, IL10RB, IL20RA, and / or IL20RB proteins, and can be used as an animal model for studying the signal mechanism of IL22, IL22RA1, IL10RB, IL20RA, and / or IL20RB and screening drugs for related diseases, demonstrating application value for the research and development of new drugs targeting immune targets.

The present invention provides a non-human animal with humanized TGFBR2 gene and its construction method, a humanized TGFBR2 protein, a humanized TGFBR2 gene, a targeting vector for TGFBR2 gene, a cell with humanized TGFBR2 gene and its application in the biomedical field. The construction method includes introducing a nucleotide sequence encoding human TGFBR2 protein into the genome of a non-human animal by means of homologous recombination. The human or humanized TGFBR2 protein can be normally expressed in this animal, which can be used as an animal model for studying the signal mechanism of human TGFBR2, screening drugs for tumors and immune-related diseases, and has important application value for the research and development of new drugs targeting immune targets.

To provide methods and compositions for modulating a target genome.SOLUTION: The present disclosure relates to compositions, systems, and methods for targeting, editing, modifying, or manipulating DNA sequences (e.g., inserting a heterologous DNA sequence of interest at a target site in a mammalian genome) at one or more locations within the DNA sequence in a cell, tissue, or subject, e.g., in vivo or in vitro. The DNA sequence of interest may include, for example, a coding sequence, a regulatory sequence, or a gene expression unit. More specifically, the present disclosure provides a retrotransposon-based system for inserting a sequence of interest into a genome.SELECTED DRAWING: None

To provide methods and compositions for modulating a target genome.SOLUTION: The present disclosure relates to compositions, systems, and methods for targeting, editing, modifying, or engineering a DNA sequence (e.g., inserting a heterologous DNA sequence of interest into a target site of a mammalian genome) at one or more locations within a DNA sequence in a cell, tissue, or subject, e.g., in vivo or in vitro. The DNA sequence of interest may comprise, for example, a coding sequence, a regulatory sequence, a gene expression unit.SELECTED DRAWING: None

Provided herein are methods for predicting unobserved phenotypes and selecting genetic variant organisms for effective use in genetically improving non-human animal species. Also provided herein are systems for implementing such methods, as well as computer-readable storage media storing instructions for performing such methods.

The invention discloses a construction method and application of an IL22 gene humanized animal, and relates to the technical field of biology. The construction method is characterized in that a whole genome sequence of exons 1-5 of a non-human animal Il22 gene is replaced by a whole genome sequence of exons 1-5 of a human IL22 gene, and a non-human animal genome contains a human sequence shown as SEQ ID NO.4. The construction method comprises the following steps: firstly, constructing a human-derived sequence; an ideal in-vivo research platform is provided for deeply researching a human IL22 signal channel mechanism and screening tumor and immune disease treatment medicines.

The invention discloses an sgRNA combination of a specific target chicken TRAPPC6A gene and application, and belongs to the technical field of animal genome editing. According to the invention, aiming at the structural characteristics of a chicken TRAPPC6A gene, two sgRNAs are optimally designed, and the two sgRNAs comprise a TRAPPC6A-sgRNA1 and a TRAPPC6A-sgRNA2; the nucleotide sequence of the TRAPPC6A-sgRNA1 is as shown in SEQ ID No. 1 (sequence identifier number 1); the nucleotide sequence of the TRAPPC6A-sgRNA2 is as shown in SEQ ID No. 2 (Sequence Identifier Number 2). A co-transfection strategy that two sgRNAs are respectively constructed in independent expression vectors is adopted, so that efficient knockout of the chicken TRAPPC6A gene is realized.

The invention provides an ERBB gene humanized non-human animal and a construction method thereof, a humanized ERBB protein, a humanized ERBB gene, a targeting vector of the ERBB gene and application of the targeting vector in the field of biological medicine, and a nucleotide sequence for coding the human ERBB protein is introduced into a non-human animal genome in a homologous recombination mode; the human or humanized ERBB protein can be normally expressed in the animal body, and the human or humanized ERBB protein can be used as an animal model for human ERBB signal mechanism research and inflammation, tumor or immune related disease drug screening, and has important application value for new drug research and development of immune targets.

A method of modifying copy (1) and copy (2) of the β2-microglobulin (β2M) gene of a porcine donor animal, genetically modified porcine donor animal wherein copy (1) and copy (2) of the β2M gene of the porcine donor animal genome are modified, and a method of producing a donor porcine donor animal tissue or organ for xenotransplantation, wherein copy (1) and copy (2) of the β2M gene of the cells of said donor porcine donor animal are modified. A method of humanizing a genetically engineered donor animal by modification of the donor animal's expressed native β2-microglobulin protein through genetic alterations of the endogenous β2M genes, and as a result, the newly expressed β2M protein of the donor animal would contain some or all of the amino acids of the orthologous human β2-microglobulin (hβ2M) protein, in identity and orientation. This results in immune-compatible xenotransplants between donor animals and human recipients.

The invention relates to a method for constructing a retinitis pigmentosa (RP) animal model. The method comprises the step of introducing PRPF31 mutation into an animal genome. The invention also relates to the RP animal model constructed by the method and application of the animal model in evaluating the efficacy and / or safety of a gene therapy drug for treating RP in vivo.

The present invention provides a method for constructing a non-human animal with a humanized CD70 gene, wherein a nucleotide sequence encoding a human CD70 protein is introduced into the non-human animal genome by homologous recombination, and the animal can normally express human or humanized CD70 protein in vivo, and can be used as an animal model for studying the human CD70 signaling mechanism, screening drugs for tumors and immune-related diseases, and has important application value for the development of new drugs for immune targets. The present invention also provides a humanized CD70 protein, a humanized CD70 gene, a targeting vector for the CD70 gene, and the application of the above-constructed non-human animal in the field of biomedicine.

The present invention provides a non-human animal with humanized TREM1 gene, a method for constructing the same, a humanized TREM1 protein, a humanized TREM1 gene, a targeting vector for TREM1 gene and its application in the field of biomedicine. By means of homologous recombination, the nucleotide sequence encoding human TREM1 protein is introduced into the genome of the non-human animal, and the human or humanized TREM1 protein can be normally expressed in the animal body. It can be used as an animal model for studying the signal mechanism of human TREM1, screening drugs for inflammation, tumors or immune-related diseases, and has important application value for the research and development of new drugs for immune targets.

The present invention provides a non-human animal with a humanized NKP46 gene and a construction method thereof, a humanized NKP46 protein, a humanized NKP46 gene, a targeting vector, and the non-human animal obtained by the above construction method and its application in the field of biomedicine. The non-human animal utilizes homologous recombination to introduce a nucleotide sequence encoding a human NKP46 protein into the genome of the non-human animal. The animal can normally express the humanized NKP46 protein in the body and can serve as an animal model for studying the human NKP46 signaling mechanism and screening drugs for tumors and immune-related diseases, and has important application value for the development of new drugs for immune targets.

To provide a gene-modified non-human animal which exerts a human EPO from an animal genome, and a method for creating the non-human animal.SOLUTION: There is provided a mouse for exerting human EPO protein (hEPO) which is created by: a process for making a nucleic acid sequence including a coding sequence or its segment which is functionally connected to an EPO promoter sequence contact with a mouse pluripotent stem cell, being a process for forming a cassette in which sequences in which the coding sequence and the promoter sequence are homologous with an endogenous mouse EPO gene locus adjacently contact with each other; a process for cultivating the pluripotent stem cell under a condition that the integration of the nucleic acid sequence to a mouse genome at the endogenous mouse EPO gene locus caused by a homologous recombination is promoted; and a process for creating a mouse from the mouse pluripotent stem cell including the nucleic acid sequence for coding the hEPO.SELECTED DRAWING: Figure 2

The present application relates to the field of animal genomic breeding technology, and particularly relates to a method suitable for cross-population joint genetic evaluation. The method obtains porcine genotype data and phenotype data from multiple source populations, infers population structure by using an unsupervised genomic stratification method, and divides the individuals to be evaluated into multiple genetically homogeneous subpopulations; based on the inferred population structure, a double random genetic effect linear mixed model is constructed, wherein the first random genetic effect is used to represent the genomic effect shared among different subpopulations, and the second random genetic effect is used to represent the subpopulation-specific deviation effect of each subpopulation relative to the shared genomic effect; the shared genomic effect and the subpopulation-specific deviation effect are predicted respectively, and the sum of the two is determined as the genomic estimated breeding value of the individual. The present application can utilize the genetic information of multiple populations without pre-specifying population labels, and improve the accuracy of genetic evaluation of important economic traits of pigs.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized MYOC locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized MYOC locus express a human myocilin protein or a chimeric myocilin protein, fragments of which are from human myocilin. Methods are provided for using such non-human animals comprising a humanized MYOC locus to assess in vivo efficacy of human-myocilin-targeting reagents and reagents for treating glaucoma.

A disposable cartridge comprising a sample receiving chamber for receiving a human or animal sample and an analysis unit (AU) having a multiplicity of reaction sites for providing a detectable indication of the presence in said sample of (a) one or more viral or bacterial nucleic acid sequences; and (b) one or more defined single nucleotide polymorphisms in the human or animal genome.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized stathmin-2 (STMN2) locus and methods of making and using such non- human animal genomes, non-human animal cells, and non-human animals are provided. Non- human animal cells or non-human animals comprising a humanized STMN2 locus express a human STMN2 mRNA and a human stathmin-2 or a humanized stathmin-2. Optionally, non- human animal genomes, non-human animal cells, and non-human animals can further comprise a mutated Tardbp locus. Methods are provided for using such non-human animals comprising a humanized STMN2 locus to assess agents as regulators of human STMN2 mRNA splicing. Agents that affect splicing of STMN2 mRNA may be useful as amyotrophic lateral sclerosis (ALS) therapeutics.

The present invention provides a non-human animal with humanized VEGFR2 gene and a construction method thereof, wherein a nucleotide sequence encoding part of the human VEGFR2 protein is introduced into the non-human animal genome by homologous recombination, and the humanized VEGFR2 protein can be normally expressed in the animal, and the animal can be used as an animal model for the study of human VEGFR2 signal mechanism, and the screening of drugs for tumor and immune-related diseases, and has important application value for the development of new drugs for immune targets. The present invention also provides a humanized VEGFR2 protein, a humanized VEGFR2 gene, a targeting vector, and a non-human animal obtained by the above construction method and its application in the field of biomedicine.

The present invention relates to humanized SIRPα-IL15 knock-in mice and methods of using them. Genetically modified non-human animals expressing human SIRPα and human IL-15 from non-human animal genomes are provided. Methods for preparing non-human animals expressing human SIRPα and human IL-15 from non-human animal genomes, and methods of using non-human animals expressing human SIRPα and human IL-15 from non-human animal genomes are also provided. These animals and methods have many uses in the art, including, for example, modeling human T cell and / or natural killer (NK) cell development and function, modeling human pathogen infection of human T cells and / or NK cells, and various in vivo screenings.

Provided is a method for constructing a retinitis pigmentosa (RP) animal model. The method comprises: incorporating, into an animal genome, a human RPGR gene fragment comprising a mutation in an RPGR gene. Further provided are an RP animal model constructed by means of the method and a use of the animal model in evaluating in vivo the efficacy and / or safety of a gene editing drug for treating RP.